This invention relates to a chemical process for the purification of rapamycin.
Rapamycin is a macrocyclic triene antibiotic produced naturally by Streptomyces hygroscopicus. It has been found useful in an array of applications based on its antitumoral and immunosuppressive effects. Uses include preventing or treating systemic lupus erythematosis, pulmonary inflammation, insulin dependent diabetes mellitus, smooth muscle cell proliferation and intimal thickening following vascular surgery, adult T-cell leukemia/lymphoma, and ocular inflammation. Rapamycin and rapamycin derivatives continue to be studied for treatment of these and other conditions.
Isomers of rapamycin are known which have structures below, referred to herein as Isomer B and Isomer C:

Conventional production of rapamycin is by way of fermentation. The fermentation process yields a low grade rapamycin product containing impurities, which is often colored (including troublesome yellow color), as opposed to a pure white product. Current purification methods require isopropanol recrystallization and/or charcoal treatment methods. The product obtained by these methods has a purity of approximately 94% (based on the sum of the individual purities of isomers B and C), and a yellow index of about 2. Repeated recrystallizations are often necessary to increase rapamycin purity, reduce the yellow index and increase the low B:C isomeric ratio to meet a minimum of approximately 23:1, resulting in low yields upon crystallization. As a result, production costs remain high.
What is needed is a chemical purification process to increase yield of rapamycin having sufficient purity and yield to meet quality and regulatory standards for pre-clinical and commercial use.